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Die vorliegende Arbeit geht hervor aus dem Hauptseminar „Argumentationstheorie“, das im Wintersemester 2008/09 am Institut für Linguistik der Universität zu Köln unter der Leitung von PD Dr. Leila Behrens abgehalten wurde. Ziel dieses Seminars war es, ausgehend von traditionellen Begriffen der Rhetorik, Dialektik und Logik, in die Terminologie sowie in zentrale Modelle der zeitgenössischen Argumentationsforschung einzuführen. Die dabei erworbenen Kenntnisse sollen im Folgenden bei der Analyse von Beiträgen eines Diskussionsforums im Internet angewendet werden. Hierbei handelt es sich um ein sogenanntes „newsforum“ der BBC mit dem Titel „Have Your Say“ (BBC 2008), in dem aktuelle Themen und Nachrichten von Internetnutzern weltweit diskutiert werden können. Im untersuchten Fall behandeln wir die Frage, wie mit der Unabhängigkeitserklärung des Kosovo vom 17. Februar 2008 umzugehen sei: „Should the world recognise an independent Kosovo?“ […]. Zu dieser Fragestellung wurden insgesamt 3195 Beiträge im Forum veröffentlicht, von denen hier 780 ausgewertet werden. Diese folgen chronologisch aufeinander und umfassen den Zeitraum zwischen 7:49 Uhr (mittlere Greenwich-Zeit) und 14:26 Uhr des 17. Februar 2008.
Leukemia cells reciprocally interact with their surrounding bone marrow microenvironment (BMM), rendering it hospitable to leukemia cell survival, for instance through the release of small extracellular vesicles (sEVs). In contrast, we show here that BMM deficiency of pleckstrin homology domain family M member 1 (PLEKHM1), which serves as a hub between fusion and secretion of intracellular vesicles and is important for vesicular secretion in osteoclasts, accelerates murine BCR-ABL1+ B-cell acute lymphoblastic leukemia (B-ALL) via regulation of the cargo of sEVs released by BMM-derived mesenchymal stromal cells (MSCs). PLEKHM1-deficient MSCs and their sEVs carry increased amounts of syntenin and syndecan-1, resulting in a more immature B-cell phenotype and an increased number/function of leukemia-initiating cells (LICs) via focal adhesion kinase and AKT signaling in B-ALL cells. Ex vivo pretreatment of LICs with sEVs derived from PLEKHM1-deficient MSCs led to a strong trend toward acceleration of murine and human BCR-ABL1+ B-ALL. In turn, inflammatory mediators such as recombinant or B-ALL cell–derived tumor necrosis factor α or interleukin-1β condition murine and human MSCs in vitro, decreasing PLEKHM1, while increasing syntenin and syndecan-1 in MSCs, thereby perpetuating the sEV-associated circuit. Consistently, human trephine biopsies of patients with B-ALL showed a reduced percentage of PLEKHM1+ MSCs. In summary, our data reveal an important role of BMM-derived sEVs for driving specifically BCR-ABL1+ B-ALL, possibly contributing to its worse prognosis compared with BCR-ABL1− B-ALL, and suggest that secretion of inflammatory cytokines by cancer cells in general may similarly modulate the tumor microenvironment.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.